Skip to main content
SpringerLink
Log in

Selective COX-2 Inhibition Is Associated with Decreased Mucosal Damage Induced by Acid and Pepsin in Rabbit Esophagitis

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Objective: To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits. Methods: Both high- and low-grade esophagitis were induced in rabbits by the perfusion of acidified pepsin. Rabbits were treated with either a selective COX-2 inhibitor (DFU[3-(3-Fluorophenyl)-4-(4-Methanesulfonyl)-5,5-Dimethyl-5H-Furan-2-One];30mg/Kg/day), a nonspecific COX inhibitor (indomethacin; 2 mg/Kg/day), or a COX-1 preferential inhibitor (piroxicam; 2 mg/Kg/12 h). Results: Prostaglandins are derived from COX-1 activity in the normal esophagus. Both low- and high-grade esophagitis are associated with a progressive increase of COX activity, which is partially dependent on the COX-2 isoform. DFU reduced muscosal damage in both models of esophagitis. However, indomethacin did not affect significantly mucosal damage, and piroxicam increased damage in low-grade esophagitis. Conclusions: COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin. Treatment with the COX-2 inhibitor DFU is associated with improvement of mucosal damage, which may have therapeutic implications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Santucci, L. L. Patoia, F. Fiorucci, D. Favoro, and A. Morelli. 1990 Oesophageal lesions during treatment with piroxicam (Letter). B. M. J. 300:1018.

    Google Scholar 

  2. Lanas, A. and B. I. Hirschowitz. 1991. Significant role of aspirin use in patients with esophagitis. J. Clin. Gastroenterol. 13:622-627.

    Google Scholar 

  3. El-Serag, H. B. and A. Sonnenberg. 1997. Association of esophagitis and esophageal strictures with diseases treated with nonsteroideal antiinflammatory drugs. Am. J. Gastroenterol. 92:52-56.

    Google Scholar 

  4. Stein, B. E., M. L. Schwartzman, M. A. Carroll, R. E. Stahl, and W. S. Rosenthal. 1989. Role of arachidonic acid metabolites in acidpepsin injury to rabbit esophagus. Gastroenterology. 97:278-283.

    Google Scholar 

  5. Eastwood, G. L., B. D. Beck, D. O. Castell, F. C. Brown, and J. R. Fletcher. 1981. Beneficial effect of indomethacin on acid-induced esophagitis in cats. Dig. Dis. Sci. 26:601-608.

    Google Scholar 

  6. Tochner, Z., M. Barnes, J. B. Mitchell, K. Orr, E. Glatstein, and A. Russo. 1990. Protection by indomethacin against acute radiation esophatitis. Digestion. 47:81-87.

    Google Scholar 

  7. Northway, M. G., G. L. Eastwood, H. I. Libshitz, M. S. Feldman, J. J. Mamel, and I. A. Szwarc. 1982. Antiinflammatory agents protect opossum esophagus during radiotherapy. Dig. Dis. Sci. 27:923-928.

    Google Scholar 

  8. Kahrilas, P. J. and W. J. Hogan. 1993. Gastroesophageal reflux disease. In: Gastrointestinal Diseases, Sleisenger, M. H. and J. S. Fordtan, eds. Philadelphia: Saunders, Volume 1, pp. 378-401.

    Google Scholar 

  9. Ismail-Beigi, F., P. F. Horton, and C. E. Pope. 1970. Histological consequences of gastroesophageal reflux in men. Gastroenterology, 58:163-174.

    Google Scholar 

  10. Ismail-Beigi, F. and C. E. Pope. 1974. Distribution of the histological changes of gastroesophageal reflux in the distal esophagus of man. Gastroenterology 66:1109-1113.

    Google Scholar 

  11. Simon, L. S. 1999. Role and regulation of Cyclooxigenase-2 during inflammation. Am. J. Med. 160(5B):37S-42S.

    Google Scholar 

  12. Lanas, A., Y. Royo, J. Ortego, M. Molina, and R. Sainz. 1999. Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis. Gastroenterology. 116(1):97-107.

    Google Scholar 

  13. Arceiz, E., A. Lanas, J. Ortego, and R. Sainz. 1997. Platelet-derived growth factor reverses the effects induced by NSAIDS on ulcer healing. Eur. J. Gastroenterol. Hepatol. 9(12):1179-1184.

    Google Scholar 

  14. Arroyo, M. T.,A. Lanas, and R. Sainz. 2000. Prevention and healing of indomethacin-induced gastric lesions: effects of ebrotidine, omeprazole and ranitidine. Eur. J. Gasterenterol. Hepatol. 12(3):313-318.

    Google Scholar 

  15. Kobayashi, S. and T. Kasuagi. 1974. Endoscopic and biopsy criteria for the diagnosis of esophagitis with a fiberoptic esophagoscope. Am. J. Dig. Dis. 19:345-352.

    Google Scholar 

  16. Lewin, K. J., R. H. Ridell, and W. M. Weinstein. 1992. Gastrointestinal pathology and its clinical implications. Volume 1. New York: Igaku-Shoin, 404-411.

    Google Scholar 

  17. Powell, W. S. 1986. Reversed-phase high-pressure liquid chromatography of araquidonic acid metabolites formed by cyclooxygenase and lipooxygenase. Anal. Bioch. 154:332-337.

    Google Scholar 

  18. Mizuno, H., C. Sakamoto, K. Matsuda, K. Wada, T. Uchida, H. Noguchi, T. Akamatsu, and M. Kasuga. 1997. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology. 112:387-397.

    Google Scholar 

  19. Soteras, F., A. Lanas, I. Fitene, Y. Royo, P. Jimenez, P. Iñarrea, J. Ortego, and F. Esteva. 2000. Nitric oxide and superoxide anion in low grade esophagitis induced by acid and pepsin in rabbits. Dig. Dis. Sci. 45:1802-1809.

    Google Scholar 

  20. Riendeau, D., M. D. Percival, S. Boyce, S. Brideau, S. Charleson, and W. Cromlish, et al. 1997. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br. J. Pharmacol. 121:105-117.

    Google Scholar 

  21. Jimenez, P., A. Lanas, E. Piazuelo, G. Bioque, and F. Esteva. 1997. Prostaglandin E2 is the major arachidonic acid metabolite secreted by esophageal mucosal cells in rabbits. Inflammation. 21(4):419-429.

    Google Scholar 

  22. Ottignon, Y., D. Alber, C. Moussard, J. P. Deschamps, P. Carayon, and J. C. Henry. 1987. Esophageal mucosal prostaglandin E2 levels in health and in gastroesophageal reflux disease. Prostaglandins Leukot. Med. 29(2-3):141-151.

    Google Scholar 

  23. Goddard, P. J., Y. J. Kao, and L. M. Lightenberger. 1990. Luminal surface hydrophobicity of canine gastric mucosa is dependent on a surface mucous gel. Gastroenterology. 98:361-370.

    Google Scholar 

  24. Wallace, J. L., C. M. Keenan, and D. N. Granger. 1990. Gastric ulceration induced by nonsteriodal antiinflammatory drugs is a neutrophil-dependent process. Am. J. Physiol. 259:G462-G467.

    Google Scholar 

  25. Needleman, P. and P. C. Isakson. 1997. The discovery and function of COX-2. J. Rheumatol. 24Suppl. 49:6-8.

    Google Scholar 

  26. Reuter, B. K., S. Asfaha, A. Buret, K. A. Sharkey, and J. L. Wallace. 1996. Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2. J. Clin. Invest. 98:2076-2085.

    Google Scholar 

  27. Wilson, K. T., S. Fu, K. S. Ramanujan, and S. J. Meltzer. 1998. Increased expression of nitric oxide shyntase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Research. 58:2929-2934.

    Google Scholar 

  28. Shrivani, V. N., R. Ouatu-Lascar, B. S. Kaur, M. B. Omary, and G. Triadafilopoulos. 2000. Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology. 118:487-496.

    Google Scholar 

  29. Morris, C. D., G. R. Armstrong, G. Bigley, H. Green, and S. E. Attwood. 2001. Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Am. J. Gastroenterol. 96(4):990-996.

    Google Scholar 

  30. Lanas. A., F. Soteras, P. Jimenez, I. Fiteni, E. Piazuelo, Y. Royo, J. Ortego, P. Iñarrea, and F. Esteva. 2001. Superoxide anion and nitric oxide in high grade esophagitis induced by acid and pepsin in rabbits. Dig. Dis. Sci. 46:2733-2743.

    Google Scholar 

  31. Patrignani, P., M. R. Panara, A. Greco, O. Fusco, C. Natoli, S. Iacobelli, and R. Cipollone, et al. 1994. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J. Pharmacol. Exp. Ther. 271(3):1705-1712.

    Google Scholar 

  32. Hayllar, J. and I. Bjarnason. 1995. NSAIDs, COX-2 inhibitors, and the gut. Lancet. 26; 346(8974:521-522.

    Google Scholar 

  33. Crofford, L. J., P. E. Lipsky, P. Brooks, S. B. Abramson, L. S. Simon, and L. B. A. Putte. 2000. Basic biology and clinical application of specific cyclooxygenase-2 inhibitors. Arthritis Rheum. 43(1):4-13.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service of Digestive Diseases, Unit of Gastrointestinal Research, University Hospital, Unidad Mixta de Investigación, Zaragoza, Spain

    Angel Lanas, Pilar Jiménez, Angel Ferrández, Alfredo Escartín & Juan Arenas

  2. The Service of Gastroenterology, University Hospital "Lozano Blesa,", 50009, Zaragoza, Spain

    Angel Lanas

  3. Service of Biochemistry, Unit of Gastrointestinal Research, University Hospital, Unidad Mixta de Investigación, Zaragoza, Spain

    Francisco Esteva

  4. Service of Pathology, Unit of Gastrointestinal Research, University Hospital, Unidad Mixta de Investigación, Zaragoza, Spain

    Javier Ortego

Authors
  1. Angel Lanas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pilar Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angel Ferrández
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alfredo Escartín
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan Arenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Francisco Esteva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Javier Ortego
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lanas, A., Jiménez, P., Ferrández, A. et al. Selective COX-2 Inhibition Is Associated with Decreased Mucosal Damage Induced by Acid and Pepsin in Rabbit Esophagitis. Inflammation 27, 21–29 (2003). https://doi.org/10.1023/A:1022635127814

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022635127814

Search

Navigation